Inflammatory signaling in skin

Inflammatory signaling in skin encompasses multiple interconnected pathways, including NF-κB/RIG-I, JAK-STAT, MAPK, mTOR, TGF-β, IL-23/IL-17, and AP-1 (Fos/Jun), that drive cytokine production (e.g., IL-1β, IL-6, IL-17, TNF-α) and chemokine release in keratinocytes, fibroblasts, and immune cells. These pathways promote chronic inflammation, cellular senescence via senescence-associated secretory phenotype (SASP), and metabolic shifts like lactate production fueling T cell activity, contributing to skin barrier dysfunction and hyperproliferation. In diseases like psoriasis, atopic dermatitis, and hidradenitis suppurativa, hyperactivation of IL-17/HIF-1α or NLRP3 inflammasomes amplifies Th17 responses and pyroptosis, while inflammageing involves age-related ROS and DNA damage triggering NF-κB and mTOR. Therapeutically, drugs target these axes—e.g., IL-17/IL-23 monoclonal antibodies reduce lesions by blocking downstream NF-κB/MAPK signaling, and experimental HIF-1α inhibitors outperform topicals in gene modulation. Challenges include balancing anti-inflammatory benefits against impaired repair or systemic immunosuppression, with ongoing research into natural modulators like AMPK activators.

Other names

Skin inflammation pathwaysinflammageing signaling pathwaysNF-κB signalingJAK-STAT pathwayMAPK pathwayIL-23/IL-17 axisAP-1 (Fos/Jun) signaling

Inhibition of IL-17 pathway to reduce keratinocyte proliferation and chemokine release, Blockade of IL-23 to suppress Th17 cell activation, NF-κB inhibition to decrease cytokine production (TNF-α, IL-6), mTOR inhibition to attenuate senescence-associated secretory phenotype (SASP), HIF-1-alpha inhibition to disrupt metabolic support for inflammation